Pain Medicine 2010; 11: 781–784

Wiley Periodicals, Inc.

Case Reports
Misdiagnosed Chronic Pelvic Pain: Pudendal
Neuralgia Responding to a Novel Use of
Palmitoylethanolamide pme_823 781..784

Rocco Salvatore Calabrò, MD, Giuseppe Gervasi, frequency, erectile dysfunction, and pain after sexual

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MD, Silvia Marino, MD, Pasquale Natale Mondo, intercourse).
MD, and Placido Bramanti, MD
Patients typically present with pain in the labia or penis,
IRCCS Centro Neurolesi “Bonino-Pulejo,” Messina, Italy perineum, anorectal region, and scrotum, which is aggra-
vated by sitting, relieved by standing, and absent when
Reprint requests to: Rocco Salvatore Calabrò, MD, via recumbent or when sitting on a lavatory seat. In the
Palermo, Cda Casazza, Messina. Tel: 390903656722; absence of pathognomonic imaging, laboratory, and elec-
Fax: 390903656750; E-mail: roccos.calabro@ trophysiology criteria, the diagnosis of PN remains primarily
centroneurolesi.it. clinical [1], and it is often delayed. Furthermore, this condi-
tion is frequently misdiagnosed and sometimes results in
unnecessary surgery. Here in we describe a 40-year-old
man presenting with chronic pelvic pain due to pudendal
Abstract nerve entrapment, misdiagnosed as chronic prostatitis.

Background. Pudendal neuralgia is a cause of After different uneffective pharmacological therapies,

chronic, disabling, and often intractable perineal the patient was treated with palmitoylethanolamide (PEA),
pain presenting as burning, tearing, sharp shooting, an endogenous lipid with antinociceptive and anti-
foreign body sensation, and it is often associated inflammatory properties [2,3] with significant improvement
with multiple, perplexing functional symptoms. of his neuralgia.

Case Report. We report a case of a 40-year-old man

Case Report
presenting with chronic pelvic pain due to pudendal
nerve entrapment and successfully treated with
A 40-year-old healthy man developed since 5 years a
palmitoylethanolamide (PEA).
progressive predominantly left-sided perineal pain
described as burning sensation. Initially, the patient expe-
Conclusion. PEA may induce relief of neuropathic
rienced the pain only in the sitting position, but pain gradu-
pain through an action upon receptors located on
ally became continuous and extended to penis. Moreover,
the nociceptive pathway as well as a more direct
it was often referred as deeper in the anorectal region (as
action on mast cells via an ALIA (autocoid local
a feeling of “foreign body”) and sometimes in distal
injury antagonism) mechanism.
urethra. Pain was exacerbated while sitting, relieved while
standing, and nearly absent when recumbent or sitting in
As recently demonstrated in animal models, the
a toilet seat. Furthermore, in some circumstances, pain
present case suggests that PEA could be a valuable
was associated to painful ejaculation, erectile dysfunction,
pharmacological alternative to the most common
urge incontinence, and dysuria. The patient also referred
drugs (anti-epileptics and antidepressants) used in
intolerance to tight clothes and underwear. Over this long
the treatment of neuropathic pain.
period, he saw many different health care professionals
(family practitioners, urologists, neurologists, and psychia-
Key Words. PEA; Pudendal Neuralgia; Chronic Pain
trists), and he was given different diagnoses (abacterial
chronic prostatitis, prostatodynia, idiopathic proctalgia,
Introduction coccygodynia, and psychogenic pain).

Pudendal neuralgia (PN) is a cause of chronic, disabling, Urinalysis with culture, semen analysis, sexual hormones
and often intractable perineal pain and it is mostly due to blood level, pelvic, and transrectal prostatic ultrasounds
pudendal nerve entrapment. were normal. As chronic pelvic pain syndrome was
supposed, he was treated with several drugs such
Neuropathic pain is referred as burning, tearing, sharp as antibiotics (ciprofloxacin, levofloxacine, gentamicin,
shooting, and foreign body sensation in the distribution azitromycine, and trimethoprim/sulfamethoxazole), antimi-
of the pudendal nerve and it is often associated with cotics (fluconazole), and anti-inflammatories (nimesulid,
multiple, perplexing functional symptoms (i.e., urinary corticosteroids) with only transient mild relief.

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Calabrò et al.

At our evaluation, the patient’s physical and neurological Table 1 Nantes criteria, September 23–24, 2006
examinations were unremarkable with the exception of a
mild hyperesthesia in the perineal area during the pinprick Diagnostic Criteria for Pudendal Neuralgia by
sensory test. Interestingly, digital rectal exploration evi- Pudendal Nerve Entrapment
denced unilateral perineal and rectal pain after pressure on
the left ischial spine. The personal history (the patient was A. Essential criteria
an amateur bicycler and regularly attended a fitness/body- Pain in the territory of the pudendal nerve: from
building center) and the neuropathic pain features, also the anus to the penis or clitoris
reproduced during rectal exam, led us to the diagnosis of Pain is predominantly experienced while sitting
PN probably secondary to nerve compression. Pain was The pain dose not wake the patient at night
rated by the patient at 8 on the 0–10 visual analog scale Pain with no objective sensory impairment
Pain relieved by diagnostic pudendal nerve block

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(VAS). Magnetic resonance imaging of the pelvic area
failed to point out organic lesions of the nerve trunk. B. Complementary diagnostic criteria
Pudendal somatosensory evoked potentials and bulb- Burning, shooting, stabbing pain, numbness
ocavernosus reflex with the electromyography of the Allodynia or hyperpathia
pelvic floor musculature showed denervation activity of the Rectal or vaginal foreign body sensation
anal sphincter. Thus, the patient was treated with pre- (sympathalgia)
gabalin, up to 150 mg/day, prematurely withdrawn Worsening of pain during the day
because of significant side effects. As the patient refused Predominantly unilateral pain
any other specific pharmacological pain treatment (i.e., Pain triggered by defecation
antidepressants and anti-epileptics), PEA, up to 900 mg/ Presence of exquisite tenderness on palpation of
day, was introduced with a significant improvement of his the ischial spine
neuralgia and associated symptoms. Clinical neurophysiology findings in men or
nulliparous women
Discussion
C. Exclusion criteria
The pudendal nerve is a mixed nerve (motory, sensory, Exclusively coccygeal, gluteal, pubic, or
and autonomic) composed of three branches: dorsal hypogastric pain
nerve of penis/clitoris, perineal nerve, and inferior anal Pruritus
nerve, all derived from sacral S2-S4 roots. It supplies the Exclusively paroxysmal pain
anal and urethral sphincters and pelvic floor muscles and Imaging abnormalities able to account for the pain
provides anal, perineal, and genital sensitivity. Pudendal D. Associated signs not excluding the diagnosis
nerve entrapment at different levels (ischial spine, sacros- Buttock pain on sitting
pinous, and sacrotuberous ligament, Alcock’s canal) is a Referred sciatic pain
cause of disabling, chronic, and intractable pelvic pain that Pain referred to the medial aspect of the thigh
is eminently variable and complex as it is often associated Suprapubic pain
with multiple, perplexing functional symptoms. Urinary frequency and/or pain on a full bladder
Pain occurring after ejaculation
In our patient, the delay of diagnosis was probably due to Dyspareunia and/or pain after sexual intercourse
the complexity of urogenital symptomatology that led to a Erectile dysfunction
misdiagnosis of chronic pelvic pain syndrome, as perineal Normal clinical neurophysiology
pain was associated to erectile dysfunction, painful ejacu-
lation, and dysuria.

In the absence of pathognomonic imaging, laboratory, specificity as it remains particularly useful for assessing
and electrophysiology criteria, the diagnosis of PN is pri- motor innervations in the pudendal nerve territory before
marily clinical and empirical. Indeed, in the presence of the surgical decompression, but not for localizing the site of
essential clinical diagnostic criteria validated by a multidis- compression [5]. In our patient, ENMG of the anal sphinc-
ciplinary working party in Nantes (France) and shown in ter was abnormal confirming the diagnosis of pudendal
Table 1, PN secondary to nerve entrapment should be nerve compression.
suspected. The penile thermal threshold test could more-
over be useful to evaluate the somatosensory and auto- Indications for surgery includes a diagnosis of pudendal
nomic system functions through the sensitive small fibers entrapment failed conservative treatment (i.e., behavioral
stimulation [4]. modifications such as avoiding offending factors that
cause pain, physical therapy with specific stretches and
Diagnostic techniques, including computed tomography- exercises, and pharmacologic treatment such as anti-
guided nerve block and electroneuromyographic (ENMG) epileptics and tricyclic antidepressants) and no long-
studies can confirm the diagnosis. lasting improvement after steroid pudendal block [6].

Perineal ENMG may provide various clues in favor of the In the described case, the patient was administered pre-
diagnosis. Nevertheless, it has a limited sensitivity and gabalin for a short time, withdrawn because of significant

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 Misdiagnosed Chronic Pelvic Pain

side effects. As he refused any other specific drug, he References

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phase) with an important improvement of symptoms. for pudendal neuralgia by pudendal nerve entrapment
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[Erratum in: Neurourol Urodyn 2008;27(4):360].
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[10]. Moreover, PEA administration may evoke a relief of
7 Aloe L, Leon A, Levi-Montalcini R. A proposed auta-
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Despite its potential clinical significance, the molecular
mechanism responsible for the antinociceptive action of 9 Jaggar SI, Hasnie FS, Sellaturay S, Rice AC. The
PEA is still poorly understood. PEA has a weak affinity anti-hyperalgesic actions of the cannabinoid ananda-
for cannabinoid CB1 and CB2 receptors, thus unchar- mide and the putative CB2 receptor agonist palmi-
acterized CB2-like receptors have been supposed [13]. toylethanolamide in visceral and somatic inflammatory
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act as an enhancer of the anti-inflammatory and anti-
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type 1, and peroxisome proliferator-activated receptor g mide, has anti-allodynic and anti-hyperalgesic effects
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Our report suggests the hypothesis that PEA, an endog- 12 Darmani NA, Izzo AA, Degenhardt B, et al. Involve-
enous mediator potentially affording protection against ment of the cannabimimetic compound, N-palmitoyl-
neuropathic pain, could be a valuable alternative to the ethanolamine, in inflammatory and neuropathic
most commonly used treatments. Further studies should conditions: Review of the available pre-clinical data,
be carried out in humans to investigate the potential use of and first human studies. Neuropharmacology 2005;
PEA as therapeutic drug. 48(8):1154–63.

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13 Farquhar-Smith WP, Jaggar SI, Rice AS. Attenuation palmitoylethanolamide upon the inactivation of
of nerve growth factor-induced visceral hyperalgesia the endocannabinoid anandamide. Br J Pharmacol
via cannabinoid CB(1) and CB(2)-like receptors. Pain 2001;133(8):1263–75.
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14 Jonsson KO, Vandevoorde S, Lambert DM, Tiger G,

Fowler CJ. Effects of homologues and analogues of

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